{"title":"Akkermansia muciniphila attenuates macrophage efferocytosis to enhance anti-PD-1 efficacy in microsatellite-stable colorectal cancer.","authors":"Yu-Ting Jiang, Guang-Qi Li, Yu-Wen Zhou, Ze-Dong Jiang, Yu-Nuo Zhao, Yu Zhang, Xiao-Meng Yin, Shen Li, Huan Tong, Lu-Si Feng, Shi-Yu Wen, Xue-Yan Zhou, Ren-Wei Li, Jing-Wen Wei, Jie-Ping Qiu, Yu-Hao Wei, Ke-Qin Tan, Sheng-Xin Zhang, Hao-Rui Zhou, Jia-Qing Yang, Jing Bai, Qin Deng, Xing-Gang Yang, Xiao-Qian Yang, Yu-Sha Wang, Xia-Wei Wei, Meng Qiu, Juan Huang, Xue-Lei Ma","doi":"10.1016/j.chom.2026.09.014","DOIUrl":"https://doi.org/10.1016/j.chom.2026.09.014","url":null,"abstract":"<p><p>Approximately 85% of colorectal cancers (CRCs) are microsatellite stable (MSS) and thus exhibit intrinsic resistance to anti-programmed death-1 (PD-1) therapy. In this study, we demonstrate that oral administration of Akkermansia muciniphila (Akk) suppresses tumorigenesis and reprograms the tumor microenvironment in MSS CRC mouse models. Akk attenuates macrophage efferocytosis through the TLR2/NF-κB pathway, an effect that leads to the accumulation of apoptotic cancer cells, which activates the cGAS-STING pathway and potentiates type I interferon production. This immunostimulatory cascade activates effector CD8<sup>+</sup> T cells and enhances the response to anti-PD-1 therapy. We conducted a phase 1 trial (NCT06865521) combining Akk probiotics with PD-1 antibody in patients with metastatic MSS CRC after ≥1 prior line of therapy. The combination therapy was safe and achieved an objective response rate of 19%, with responders exhibiting enhanced antitumor immunity. Our multilevel investigation provides a promising strategy to overcome immunotherapy resistance in MSS CRC through targeted modulation of the gut microbiome.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":""},"PeriodicalIF":18.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell host & microbePub Date : 2026-10-14Epub Date: 2026-09-04DOI: 10.1016/j.chom.2026.08.010
Ying Jiao, Cillian Hao Cheng, Xiang Gao, Weixun Li, Fenfen Ji, Cong Liang, Pingmei Huang, Lok Hin Ko, Liufang Ye, Issac Chung Hin Kam, Alvin Ho-Kwan Cheung, Wei Kang, Jun Yu, Chi Chun Wong
{"title":"Bacteroides acidifaciens enriched by KRAS mutation promotes colorectal tumorigenesis.","authors":"Ying Jiao, Cillian Hao Cheng, Xiang Gao, Weixun Li, Fenfen Ji, Cong Liang, Pingmei Huang, Lok Hin Ko, Liufang Ye, Issac Chung Hin Kam, Alvin Ho-Kwan Cheung, Wei Kang, Jun Yu, Chi Chun Wong","doi":"10.1016/j.chom.2026.08.010","DOIUrl":"10.1016/j.chom.2026.08.010","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a multifactorial disease impacted by the tumor microbiome and host genetics, notably mutations that activate KRAS to stimulate a RAF-MEK-extracellular signal-regulated kinase (ERK) proliferative cascade. However, whether host genetics interplays with the tumor microbiome remains unclear. Here, we profiled intratumoral microbiomes from KRAS-mutant CRC patients and intestine-specific oncogenic KRAS<sup>G12D</sup> mice, revealing that KRAS reshapes the microbial community, enriching Bacteroides acidifaciens that predicts poor prognosis in KRAS-mutant CRC patients. Employing isogenic CRC cells and mice with or without mutant KRAS, we demonstrate that B. acidifaciens promotes malignant phenotypes in KRAS-mutant CRC cells and intestine-specific KRAS<sup>G12D</sup> mice but not in wild-type counterparts. B. acidifaciens SusF binds and stabilizes ARHGEF2, which promotes active KRAS and RAF-MEK-ERK signaling. SusF ablation or ARHGEF2 knockout in KRAS-mutant CRC cells abrogates the pro-tumorigenic effects of B. acidifaciens. These observations offer strategies for targeting mutant KRAS-driven B. acidifaciens to mitigate feedforward signaling leading to tumorigenesis.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1914-1929.e9"},"PeriodicalIF":18.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell host & microbePub Date : 2026-09-09Epub Date: 2026-07-01DOI: 10.1016/j.chom.2026.06.005
Zichen Luo, Zihan Xiao, Tianjie Yuan, Xuan Wang, Chen Shi, Weichen Xu, Ying Chong, Xionglin Hou, Peifeng Wu, Mingxiao Li, Xiaofang He, Yi Zhou, Tao Zhang, Xinyu Ji, Ke Su, Tao Chen, Xuzhuo Wang, Tong Xie, Liuqing Di, Houkai Li, Bin Xu, Haibo Cheng, Jinjun Shan
{"title":"Gut commensal Bacteroides-derived pantothenic acid alleviates metabolic syndrome.","authors":"Zichen Luo, Zihan Xiao, Tianjie Yuan, Xuan Wang, Chen Shi, Weichen Xu, Ying Chong, Xionglin Hou, Peifeng Wu, Mingxiao Li, Xiaofang He, Yi Zhou, Tao Zhang, Xinyu Ji, Ke Su, Tao Chen, Xuzhuo Wang, Tong Xie, Liuqing Di, Houkai Li, Bin Xu, Haibo Cheng, Jinjun Shan","doi":"10.1016/j.chom.2026.06.005","DOIUrl":"10.1016/j.chom.2026.06.005","url":null,"abstract":"<p><p>Pantothenic acid (PA), or vitamin B5, can be synthesized by gut commensals, but the contribution of microbial PA to metabolic health remains unclear. Here, we find that microbial PA supply is reduced in individuals with metabolic syndrome (MetS) and is associated with impaired gut barrier function and disease severity. Tracing microbial PA identifies Bacteroides fragilis as a key contributor, with panC required for PA biosynthesis, as confirmed by isotope tracing, bacterial culture, and germ-free colonization. In MetS models, colonization with wild-type, but not ΔpanC B. fragilis, restores PA, preserves gut barrier integrity, reduces endotoxemia, and improves metabolic dysfunction. Mechanistically, microbial PA requires host pantothenate kinase activity, as silencing pantothenate kinase 2/3 (PANK2/3) in colonic organoids and in vivo reduces coenzyme A (CoA)/acetyl-CoA metabolism, suppresses Krüppel-like factor 4 (KLF4)-associated differentiation programs, and blunts the protective effects of microbial PA. Finally, a plant-derived polysaccharide enriches PA-producing Bacteroides and restores colonic PA, highlighting a strategy for colonic homeostasis and metabolic health.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1764-1778.e8"},"PeriodicalIF":18.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148371353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell host & microbePub Date : 2026-09-09Epub Date: 2026-08-06DOI: 10.1016/j.chom.2026.06.018
Meng Li, Shangqi Li, Danlei Zheng, Baoying Liao, Hongjuan Niu, Yue Wang, Xiyao Liu, Heng Pan, Yang Yu, Ping Zhou, Rong Li
{"title":"Lactobacillus gasseri postbiotics ameliorate age-related decline in endometrial receptivity.","authors":"Meng Li, Shangqi Li, Danlei Zheng, Baoying Liao, Hongjuan Niu, Yue Wang, Xiyao Liu, Heng Pan, Yang Yu, Ping Zhou, Rong Li","doi":"10.1016/j.chom.2026.06.018","DOIUrl":"10.1016/j.chom.2026.06.018","url":null,"abstract":"<p><p>Endometrial senescence contributes to a decline in fertility in women of advanced reproductive age, with emerging evidence linking it to remodeling of the uterine microbiome, particularly a reduced Lactobacillus abundance. Here, using a cross-sectional human cohort with clinical follow-up, we identify an age-related shift in the endometrial microbiome, characterized by the loss of beneficial Lactobacillus-enriched states and increased Lactobacillus iners. This shift is associated with impaired endometrial receptivity and less favorable embryo transfer outcomes. Functional screening of reproductive tract isolates highlights Lactobacillus gasseri as a candidate strain with strong antioxidant, anti-inflammatory, and adhesion-related activities. In cells and mouse models, L. gasseri and its exopolysaccharides (EPSs) attenuate endometrial senescence and improve implantation in aged mice. Mechanistically, these effects are mediated, at least partly, through the modulation of Hippo-YAP signaling. These findings suggest that restoring beneficial Lactobacillus and applying EPSs may represent complementary strategies to improve endometrial function and fertility outcomes in women of advanced reproductive age.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1779-1794.e6"},"PeriodicalIF":18.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engineering oral commensal nanovaccines to activate mucosal-systemic immune cascades against tumor.","authors":"Zirong Dong, Shuyan Li, Yuning Wei, Jiaxin Zhao, Weiwen Kong, Wenjuan Liu, Jian Chen, Haisheng He, Jinlong Yang, Jianping Qi","doi":"10.1016/j.chom.2026.06.021","DOIUrl":"10.1016/j.chom.2026.06.021","url":null,"abstract":"<p><p>Mucosal immunity-the body's frontline defense, harboring 80% of the body's immune cells-represents a potent yet underexploited avenue for cancer vaccination. Here, we developed an oral biohybrid vaccine platform by integrating tumor antigen-loaded liposomes with fimbriae-enriched bacteria (Escherichia coli or VNP20009) through bacterial hitchhiking or membrane hybridization. These biohybrids promote mucosal antigen delivery via glycoprotein 2 (GP2)-mediated microfold-cell (M-cell) transcytosis, enhancing antigen cross-presentation and activation of a mucosa-periphery-tumor immune cascade. Bacterial membrane-hybridized vaccines outperform bacteria-hitchhiking counterparts by reconfiguring dendritic cell (DC) subsets within gut-associated lymphoid tissues (GALTs) and triggering C-C chemokine receptor type 7 (CCR7)-dependent immune cell trafficking, thereby propagating mucosal immune activation toward distal tumor microenvironment (TME) reprogramming and tumor control. When combined with PD-1 blockade, this strategy enhances antitumor efficacy by promoting effector cell mobilization and establishing memory against tumor rechallenge. Collectively, these findings position bacteria-derived arsenal biohybrids as a versatile oral vaccine strategy, advancing mucosal immunotherapy for cancer.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1729-1745.e10"},"PeriodicalIF":18.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148586315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell host & microbePub Date : 2026-09-09Epub Date: 2026-08-10DOI: 10.1016/j.chom.2026.07.009
Himanshu Chhillar, Leonardo Jo, Volkan Cevik, Amey Redkar, Kaisa Kajala, Jonathan D G Jones, Pingtao Ding 丁平涛
{"title":"Cell-type-specific activation of broadly perceived effector-triggered immunity restricts pathogen invasion in plants.","authors":"Himanshu Chhillar, Leonardo Jo, Volkan Cevik, Amey Redkar, Kaisa Kajala, Jonathan D G Jones, Pingtao Ding 丁平涛","doi":"10.1016/j.chom.2026.07.009","DOIUrl":"10.1016/j.chom.2026.07.009","url":null,"abstract":"<p><p>Effector-triggered immunity (ETI) is central in plant defense, but whether all cell types execute ETI similarly remains unknown. We combined chemically imposed immune activation with single-cell transcriptomics to profile ETI responses across major leaf cell types in Arabidopsis. Despite uniform ETI perception, we find divergent transcriptional outputs: a core set of defense genes is broadly induced, while distinct cell types activate specialized immune modules. We infer that immune outputs are shaped not only by immune receptor activation but also by cell identity, transcription factor availability, and chromatin accessibility. We further demonstrate that epidermis-enriched transcriptional regulators are required to restrict invasion by non-adapted pathogens. Their absence permits pathogen entry into deeper tissues despite intact recognition, revealing a spatial division of immune functions. Our findings uncover a layered immune architecture in plants, challenge the assumption of uniform immune activation, and establish a framework for exploring cell-type-specific resistance logic in multicellular hosts.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1843-1853.e4"},"PeriodicalIF":18.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell host & microbePub Date : 2026-09-09Epub Date: 2026-08-25DOI: 10.1016/j.chom.2026.07.019
Erika J Hughes, Charlie J Pyle, Mark Chambers, Jana Travnickova, Thabo Mpotje, Jacob P Lowy, Nathan T Strang, Carson E Carranza, Henry K E Ohman, Threnesan Naidoo, Liuyang Wang, Dennis C Ko, Jadee L Neff, Simon G Gregory, Clare M Smith, Jason E Stout, Fred B Lih, Matthew L Edin, Darryl C Zeldin, E Elizabeth Patton, Mohlopheni J Marakalala, Alasdair Leslie, David M Tobin
{"title":"Host eicosanoid signals define a granuloma fibroblast population that coordinates mycobacterial containment.","authors":"Erika J Hughes, Charlie J Pyle, Mark Chambers, Jana Travnickova, Thabo Mpotje, Jacob P Lowy, Nathan T Strang, Carson E Carranza, Henry K E Ohman, Threnesan Naidoo, Liuyang Wang, Dennis C Ko, Jadee L Neff, Simon G Gregory, Clare M Smith, Jason E Stout, Fred B Lih, Matthew L Edin, Darryl C Zeldin, E Elizabeth Patton, Mohlopheni J Marakalala, Alasdair Leslie, David M Tobin","doi":"10.1016/j.chom.2026.07.019","DOIUrl":"10.1016/j.chom.2026.07.019","url":null,"abstract":"<p><p>Genetic variation at the leukotriene A4 hydrolase (LTA4H) locus is associated with tuberculosis (TB) severity and outcome. Here, we define a unique population of peripheral fibroblasts at the mycobacterial granuloma, the central immune structure in TB, whose recruitment and functions are coordinated by lta4h-dependent signals. Using single-cell profiling of zebrafish mycobacterial infections, we identify a layer of lta4h-dependent recruited fibroblasts at the granuloma's edge with mesenchymal and stem-like expression signatures, including aldh1a3 expression. Ablation of these cells compromises bacterial containment at the structure's periphery. Similarly, genetic disruption of apolipoprotein D, produced specifically in granuloma-associated fibroblasts, results in an altered eicosanoid balance, decreased inflammation, and increased dissemination of infection. In humans, this granuloma-associated fibroblast population is distinct from myofibroblasts, interacts with LTA4H-expressing macrophages, and is prominent across diverse TB granuloma types. These results link a host genetic susceptibility locus to the recruitment and function of a specialized fibroblast population that limits bacterial dissemination.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1795-1813.e7"},"PeriodicalIF":18.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The genetic repertoire of deep-sea microbiome: From sequence to structure and function.","authors":"Yang Guo, Zongan Wang, Denghui Li, Lele Wang, Hongxia Lan, Fei Guo, Ziyu Zhao, Zhenjun Liu, Liang Meng, Xuechun Shen, Minxiao Wang, Weishu Zhao, Weijia Zhang, Chaodi Kong, Liuxin Shi, Ying Sun, Inge Seim, Aijun Jiang, Kailong Ma, Zidong Su, Nannan Zhang, Qianyue Ji, Junyi Chen, Ke Chen, Chen Qi, Baitao Li, Beibei He, Yuqian Liu, Jiayong Zhou, Yue Zheng, Huan Zhang, Yinzhao Wang, Mo Han, Tao Yang, Jiawei Tong, Yulu Zhang, Zhijie Wang, Xiaokai Xu, Jiayu Chen, Yue Liu, Haixin Chen, Tao Zeng, Xiaofeng Wei, Chaolun Li, Huanming Yang, Bo Wang, Xin Liu, Changwei Shao, Wenwei Zhang, Ying Gu, Xiang Xiao, Xun Xu, Jian Wang, Thomas Mock, Guangyi Fan, Yuxiang Li, Shanshan Liu, Yuliang Dong","doi":"10.1016/j.chom.2026.05.009","DOIUrl":"10.1016/j.chom.2026.05.009","url":null,"abstract":"<p><p>The deep sea, as the largest and maybe most hostile environment on Earth, is still underexplored, especially regarding its genetic repertoire. Yet, previous work has revealed significant habitat-specific deep-sea biodiversity. Here, we present an integrated deep-sea microbial genetic dataset comprising 502 million nonredundant genes from 2,138 samples and 2.4 million predicted structures and use it to link specific protein structures with genetic variants associated with life in the deep sea and to assess their biotechnology potential. Combining global sequence analysis with biophysical and biochemical measurements revealed unprecedented sequence diversity and substantial structural conservation of proteins. Especially, proteins involved in replication, recombination, and repair were identified as being under rapid evolution and with specialized properties. Among these, a structurally divergent helicase exhibited advantages in controlling nanopore sequencing speed. Thus, our work positions the deep sea as an evolutionary engine that generates and hosts genetic diversity and bridges genetic knowledge with biotechnology.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1509-1522.e10"},"PeriodicalIF":18.7,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unveiling active microbial processes in Earth's deepest seawater.","authors":"Wei-Jia Zhang, Aoran Hu, Ziheng Wu, Liangting Liu, Chen Li, Yujue Wang, Zhanfei Wei, Rui Lu, Jun Li, Yang He, Taoliang Zhang, Shanshan Liu, Jing Wang, Liang Meng, Xiang Xiao, Weishu Zhao","doi":"10.1016/j.chom.2026.07.001","DOIUrl":"10.1016/j.chom.2026.07.001","url":null,"abstract":"<p><p>Microorganisms dominate life in the hadal zone, yet extreme sampling difficulty and low biomass have precluded characterization of their in situ activities. Here, we analyze microbiome samples collected from hadal seawaters via in situ filtration during 12 human-occupied vehicle dives. DNA-protein co-extraction and metagenome-guided metaproteomic analysis identify 135,073 non-redundant active proteins, with over 95% being hadal-specific. Metaproteomic quantification distinguishes highly active and less active taxa that differ in biogeographic origins and genomic traits. Hadal microorganisms operate a metabolic regime fundamentally distinct from the upper ocean, preferentially utilizing refractory organic matter (aromatics, halogenated compounds, and D-amino acids) and expanded electron acceptors (thiosulfate and heavy metals), collectively shaping hadal element cycling. Active viruses extend beyond \"Piggyback-the-Winner\" dynamics, enhancing host adaptation through auxiliary metabolic genes. These findings provide proteome-level evidence of hadal microbial activities and reveal biogeochemical cycling distinct from that of the upper ocean, highlighting the underappreciated significance of hadal microbiomes within global ocean ecosystems.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1540-1559.e10"},"PeriodicalIF":18.7,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell host & microbePub Date : 2026-08-12Epub Date: 2026-06-23DOI: 10.1016/j.chom.2026.05.029
Christine M Tin, Bianca Cordazzo Vargas, Darryl A Abbott, Aditi R Lohar, Tiffany C Taylor, Ivan A Valishev, Sarah N Weinshel, Vung Lian, Kacey J Sullinger, Matthew Butoryak, Michael A Silverman, Liat Shenhav, William H DePas, Timothy W Hand
{"title":"Single-cell detection and quantification of the microbiota by MicFLY.","authors":"Christine M Tin, Bianca Cordazzo Vargas, Darryl A Abbott, Aditi R Lohar, Tiffany C Taylor, Ivan A Valishev, Sarah N Weinshel, Vung Lian, Kacey J Sullinger, Matthew Butoryak, Michael A Silverman, Liat Shenhav, William H DePas, Timothy W Hand","doi":"10.1016/j.chom.2026.05.029","DOIUrl":"10.1016/j.chom.2026.05.029","url":null,"abstract":"<p><p>The intestinal microbiota regulates multiple host functions, including digestion and immune development. Our knowledge of the microbiota has been shaped by available technology, which primarily measures relative abundance. Quantitative, single-cell bacterial measurements would improve our understanding of microbiome biology, including the dynamics behind shifts in microbiota composition. We present microbiota flow cytometry (MicFLY), a single-cell technology that quantifies absolute bacterial abundance with species-level resolution. Using MicFLY, we can identify the major intestinal taxa, discriminate live from dead bacteria, measure heterogeneous mRNA expression, and concurrently quantify immunoglobulin A (IgA) and IgG binding to intestinal bacteria. Using longitudinal, quantitative microbiota analyses on a small cohort of preterm infants, we find that increases in IgA- and IgG-unbound bacteria from various Enterobacteriaceae species associate with the development of necrotizing enterocolitis (NEC). MicFLY single-cell technology thus enables fine-scale quantitative microbiota measurements for a deeper mechanistic understanding of compositional changes.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1663-1679.e10"},"PeriodicalIF":18.7,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13361012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148310735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}